scholarly journals RACIPE: A computational tool for Modeling Gene Regulatory Circuits using Randomization

2017 ◽  
Author(s):  
Bin Huang ◽  
Dongya Jia ◽  
Jingchen Feng ◽  
Herbert Levine ◽  
José N. Onuchic ◽  
...  
Keyword(s):  
Kinetic Parameters ◽  
Toggle Switch ◽  
B Lymphopoiesis ◽  
Computational Tool ◽  
Regulatory Circuits ◽  
Dynamical Features ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits ◽  
Free Open Source ◽  
Insufficient Knowledge

AbstractMotivationOne of the major challenges in traditional mathematical modeling of gene regulatory circuits is the insufficient knowledge of kinetic parameters. These parameters are often inferred from existing experimental data and/or educated guesses, which can be time-consuming and error-prone, especially for large networks.ResultsWe present a computational tool based on our newly developed method named random circuit perturbation (RACIPE), to explore the robust dynamical features of gene regulatory circuits without the requirement of detailed kinetic parameters. RACIPE generates an ensemble of circuit models with distinct random parameters and uniquely identifies robust dynamical properties by statistical analysis. Here, we discuss software implementation and illustrate the usage of RACIPE on coupled toggle-switch circuits and a published circuit of B-lymphopoiesis. We expect RACIPE to contribute to a more comprehensive and unbiased understanding of gene regulatory mechanisms.AvailabilityRACIPE is a free open source software distributed under (Apache 2.0) license and can be downloaded from GitHub (https://github.com/simonhb1990/RACIPE-1.0)[email protected], [email protected] or [email protected]

scholarly journals Modeling Dynamic Transcriptional Circuits with CRISPRi

2017 ◽  
Author(s):  
Samuel E. Clamons ◽  
Richard M. Murray
Keyword(s):  
Transcriptional Repression ◽  
Pulse Generator ◽  
Toggle Switch ◽  
Regulatory Circuits ◽  
Dynamic Circuits ◽  
Degradation Rates ◽  
Highly Sensitive ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits ◽  
Simple Dynamical Model

AbstractTargeted transcriptional repression with catalytically inactive Cas9 (CRISPRi) can be used to build gene regulatory nets similar in principle to those made with traditional transcription factors, and promises to do so with better orthogonality, programmability, and extensibility. We use a simple dynamical model of CRISPRi to understand its behavior and requirements, and to show that CRISPRi can recapitulate several classic gene regulatory circuits, including the repressilator, a toggle switch, and an incoherent feed-forward loop pulse generator. Our model also predicts that these circuits are highly sensitive to promoter leak, but that promoter leak can be offset with active degradation of dCas. We provide specifications for required fold-repression and dCas degradation rates for several dynamic circuits. Our modeling reveals key engineering requirements and considerations for the construction of dynamic CRISPRi circuits, and provides a roadmap for building those circuits.

scholarly journals RACIPE: a computational tool for modeling gene regulatory circuits using randomization

2018 ◽  
Vol 12 (1) ◽  
Author(s):  
Bin Huang ◽  
Dongya Jia ◽  
Jingchen Feng ◽  
Herbert Levine ◽  
José N. Onuchic ◽  
...  
Keyword(s):  
Computational Tool ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

scholarly journals Integrated Gene Regulatory Circuits: Celebrating the 50th Anniversary of the Operon Model

2011 ◽  
Vol 43 (4) ◽  
pp. 505-514 ◽  
Author(s):  
Shahragim Tajbakhsh ◽  
Giacomo Cavalli ◽  
Evelyne Richet
Keyword(s):  
50Th Anniversary ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

scholarly journals Synthetic 5’ UTRs can either up- or down-regulate expression upon RBP binding

2017 ◽  
Author(s):  
Noa Katz ◽  
Roni Cohen ◽  
Oz Solomon ◽  
Beate Kaufmann ◽  
Orna Atar ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Cooperative Behavior ◽  
Transcriptional Level ◽  
Rna Molecules ◽  
Regulatory Modules ◽  
Regulatory Circuits ◽  
Rna Hairpins ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

SUMMARYThe construction of complex gene regulatory networks requires both inhibitory and up-regulatory modules. However, the vast majority of RNA-based regulatory “parts” are inhibitory. Using a synthetic biology approach combined with SHAPE-Seq, we explored the regulatory effect of RBP-RNA interactions in bacterial 5’-UTRs. By positioning a library of RNA hairpins upstream of a reporter gene and co-expressing them with the matching RBP, we observed a set of regulatory responses, including translational stimulation, translational repression, and cooperative behavior. Our combined approach revealed three distinct states in-vivo: in the absence of RBPs, the RNA molecules can be found either in a molten state that is amenable to translation, or a structured phase that inhibits translation. In the presence of RBPs, the RNA molecules are in a semi-structured phase with partial translational capacity. Our work provides new insight into RBP-based regulation and a blueprint for designing complete gene regulatory circuits at the post-transcriptional level.

scholarly journals The miRNA-gene regulatory circuits in nSARS-CoV-2 and their potential correlations with pulmonary and thrombotic disorders

2020 ◽  
Author(s):  
Pankaj Khurana ◽  
Apoorv Gupta ◽  
Ragumani Sugadev ◽  
Y K Sharma ◽  
Rajeev Varshney ◽  
...  
Keyword(s):  
Drug Targets ◽  
Molecular Mechanisms ◽  
Cell Cycle Control ◽  
Mirna Gene ◽  
Protein Stabilization ◽  
Common Mechanism ◽  
The Novel ◽  
Regulatory Circuits ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits

Abstract In view of the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates, diagnostic markers etc have created a new race to curb the disease. To uncover nSARS-CoV-2-related important biological features and understanding the molecular basis of this disease, network biology and miRNA-gene regulatory motif-based approach is used. 11 antiviral human-microRNAs (miRNAs) which can potentially target SARS-CoV-2 genes were collated; their direct miRNA interactors were identified and a comprehensive nSARS-CoV-2 responsive miRNA:Transcription Factor (TF):gene coregulatory network was built. 1385 miRNA:TF:gene tripartite, Feed-Forward Loops (FFLs) were identified from the network. The network topology was mapped into the biological space and the overrepresented pathways were identified. Four regulatory circuits: hsa-mir-9-5p-EP300-PLCB4, hsa-mir-324-3p-MYC-HLA-F, hsa-mir-1827-E2F1-CTSV and hsa-mir-1277-5p-SP1-CANX are identified. These miRNA-gene regulatory circuits are found to regulate signalling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. Some novel computational evidences for understanding nSARS-CoV-2 molecular mechanisms controlled by these regulatory circuits is put forth. The novel associations of miRNAs and genes identified with this infection are open for experimental validation. Further, these regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection and pulmonary diseases and thromboembolic disorders. A detailed molecular snapshot of TGF-β signalling pathway as the common mechanism that could play an important role in controlling common pathophysiology i.e. systemic inflammation, increased pulmonary pressure, ground glass opacities, D-dimer overexpression is also put forth.

scholarly journals Variation, Variegation and Heritable Gene Repression in S. cerevisiae

2021 ◽  
Vol 12 ◽  
Author(s):  
Kholoud Shaban ◽  
Safia Mahabub Sauty ◽  
Krassimir Yankulov
Keyword(s):  
Gene Expression ◽  
Current Knowledge ◽  
Regulatory Circuits ◽  
Epigenetic Diversity ◽  
Short And Long Term ◽  
Unstructured Proteins ◽  
Gene Regulatory ◽  
Gene Regulatory Circuits ◽  
Insight Into

Phenotypic heterogeneity provides growth advantages for a population upon changes of the environment. In S. cerevisiae, such heterogeneity has been observed as “on/off” states in the expression of individual genes in individual cells. These variations can persist for a limited or extended number of mitotic divisions. Such traits are known to be mediated by heritable chromatin structures, by the mitotic transmission of transcription factors involved in gene regulatory circuits or by the cytoplasmic partition of prions or other unstructured proteins. The significance of such epigenetic diversity is obvious, however, we have limited insight into the mechanisms that generate it. In this review, we summarize the current knowledge of epigenetically maintained heterogeneity of gene expression and point out similarities and converging points between different mechanisms. We discuss how the sharing of limiting repression or activation factors can contribute to cell-to-cell variations in gene expression and to the coordination between short- and long- term epigenetic strategies. Finally, we discuss the implications of such variations and strategies in adaptation and aging.

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